1. Technical Field
The disclosure relates to the non-invasive destruction of adipose tissue by using focused ultrasound (FUS). The present disclosure also relates to the improvement in treatment efficiency of the novel FUS by the combination with electrical stimulation.
2. Description of Related Art
Obesity and overweight have been clinically identified as a cause of many diseases, such as hypertension, cardiovascular diseases, and type-2 diabetes. Body Mass Index (BMI) is a measurement of obese degree and people are defined as overweight if their BMI is between 25 and 30 kg/m2, and obese when it is greater than 30 kg/m2. Centers for Disease Control and Prevention of USA report that 33.8% of U.S. adults are obese and approximately 17% (or 12.5 million) of children and adolescents aged 2-19 years are obese in 2007-2008. Moreover, obesity trend among U.S. adults is a dramatic increase from 1985 through 2010, and no state had a prevalence of obesity less than 20% in 2010 (http://www.cdc.gov/obesity/index.html).
Adipose tissue is composed of fat cells (adipocytes) in which the lipid is stored. Liposuction surgery has been used to break fat cells and then to remove the lipid by suction. However, liposuction surgery is an invasive surgery with high risk, and it needs several weeks of recovery time.
Recently, a noninvasive tumor treatment by using high-intensity focused ultrasound (HIFU) is established and affirmed clinically. In particular, said treatment for uterine fibroids is approved by the FDA in the U.S. The principles of said treatment are that the acoustic beam is generated extracorporeally by an ultrasound transducer, transmitted via a plurality of media and focused on the target region, and the high energy within the focus can be absorbed by tumor cells to form a hot spot. The temperature of the hot spot is up to 60-70° C. to cause coagulative necrosis of the tumor cells during a short time period. The necrosed cells can be cleaned naturally after treatment. Clinical trials show that more than 6,000 female patients worldwide who suffered from uterine fibroids have been treated by HIFU. Based on the treatment results and trace after surgery, the safety, effectiveness and reliability of HIFU for noninvasive tissue ablation is confirmed (F. A. Taran, et al.; for the MRgFUS group. Ultrasound in Obstetrics and Gynecology, 2009; A. Okada, et al., Ultrasound in Obstetrics & Gynecology, 2009; A. Dobrotwir and E. Pun, Journal of Medical Imaging and Radiation Oncology, 2012).
Tissue ablation by HIFU modality has been applied to cosmetic body sculpting, such as U.S. Patent Pub. No. 20080015435, which discloses a HIFU system for the destruction of adipose tissue in the human body. The system contains a plurality of sensors adopted to detect echo signals created by cavitation or boiling of organic tissue for the safety of ablation treatment. Further, a transducer of the system emits ultrasonic waves with a specific sequence of on/off cycles into organic tissue, such that heat produced at the target is not easy to be conducted away between consecutive on cycles in the sequence. The system can detect fat thickness by optical cameras and ultrasonic imaging system.
Safety of adipose cell ablation by HIFU has been confirmed in clinical trial (E. Garcia-Murray, et al., American Society of Plastic Surgeons Annual Meeting, 2005). Twenty-four patients underwent the HIFU treatment and had blood drawn at various time points as follows: before HIFU treatment, after HIFU treatment including 1, 2 and 3 day, 1-4 weeks and 1-3 months later. The blood analyses illustrate no significant changes in the level of free fatty acids, total cholesterol, very low density lipoprotein (VLDL), high density lipoprotein (HDL), low density lipoprotein (LDL) and triglyceride. At the same time, comprehensive metabolic panel, amylase, lipase and complete blood count of the 24 patients have no significant variation. Accordingly, it is believed that removing adipose tissue by HIFU can't cause acute or chronic side effect of metabolisms of lipid, free fatty acid and glucose as well as functions of liver and kidney.
With respect to therapeutic outcome, the clinical trial reports that 282 patients with average 41.3-year-old are treated by HIFU once with 45-60 minutes of treating time, and their waistline reduced 4.7 cm in average within 3 months (A. Fatemi, Seminars in Cutaneous Medicine and Surgery, 2009). The mechanism of said treatment is that HIFU destroyed a part of adipose cells to release lipid, and the destroyed cells stay with undestroyed adipose cells. In about 8 weeks later, scavenger macrophages engulf the intercellular lipids. However, about 75% of the released lipid is re-absorbed by the undestroyed adipose cells (P. B. Fodor, et al., American Society for Aesthetic Plastic Surgery Annual Meeting, 2006).
Cavitation induced by ultrasound is also used in destroying adipose tissue. Distinctive from thermal ablation of HIFU, ultrasonic cavitation generates bubble collapse within adipose tissue to destroy it. As described in U.S. Pat. No. 7,875,023, an apparatus emits a pulsed focused ultrasound with a frequency in a range of 50 KHz-1000 KHz outside of body, directs said ultrasonic energy at a target region, i.e., adipose tissue, and generates cavitation with a duty cycle between 1:2 and 1:250 to lyse adipose tissue.
Pulsed focused ultrasound is used to remove adipose tissue in more than 50 countries and the total number of said treatment is as high as 200 thousand. Safety and effectiveness have been confirmed based on treatment results from 550 patients (http://www.ultrashape.com). Waistline can be reduced 4 cm in average by three-time treatment with 30-90 minutes per treatment. Therapeutic results can be observed in 4 weeks after treatment. It is also confirmed that the released triglyceride from the patient's adipose tissue subject to pulsed focused ultrasound treatment does not significantly accumulate in the blood or liver (S. A. Teitelbaum et al., Plastic and Reconstructive Surgery, September 2007).
Accordingly, it is confirmed that destroying adipose tissue by HIFU or pulsed focused ultrasound treatment can achieve the safety and effectiveness that cosmetic body sculpting possesses. However, it needs to take 2-12 weeks to see the treatment results. Unsuitable dietary habit during this long period can easily reduce the therapy effects. Further, if the released lipid from destroyed adipose tissue is not metabolized, it will be restored to undestroyed or new adipose cells, so that the benefit of ultrasonic therapy is reduced. Further, current ultrasonic transducers can merely focus on a “point” of the target area, which causes the treated area being limited and the treating time being as long as one hour per treatment. It easily makes the patient uncomfortable and restricts the effect of body sculpting.
Lipid is a molecule for storing energy in the body. It is known from the above that the released lipid via ultrasonic treatment may be restored in undestroyed adipose tissue if it is not consumed. The way for enhancing energy consumption includes heat generation and exercise. Exercise can consume energy more efficiently while heat generation cannot be applied frequently due to the accompanying increase of body temperature. Muscle is the main motion organ of the human body and generates contraction under the voluntary control. On the other hand, muscle contraction can be induced by external stimuli like electrical current. External current flows into the body via skin and stimulates near nerves to induce muscle contraction. Since the activation threshold of the muscle is about ten times of that of a nerve, only a small electric current can be used to activate the nerve for safety. While the nerve is activated, action potential is transmitted to neuromuscular junction to trigger the entry of Ca2+ into the muscle, and then the interaction of actin and myosin is induced to form muscle contraction. ATP is essential for the interaction of actin and myosin. Maintenance of isometric contraction is an unstable dynamic balance and needs continuous ATP supply, so that a muscle cell has to produce ATP by metabolism of carbohydrates or lipids continuously.
Muscle contraction, as well as energy consumption, induced by self-consciousness control is basically the same as that by external electricity. Therefore, external electricity can be applied to consume energy. Another advantage of energy consumption by muscle contraction, compared with heat generation, is to maintain muscle status or even train the muscle to keep the body fit. Various muscles can be trained by applying electric stimulation to the various parts of muscle.
Transcutaneous electric stimulation is one of standard clinical rehabilitation techniques, which is applied to long-term bedridden patients to avoid muscle disuse atrophy. This technique is never used for increasing energy consumption. Appropriate parameters and electrical stimulation do not harm organisms and muscles or make the patient uncomfortable. Generally, the parameters including the applied electric current per unit of body surface area and the stimulation frequency should be noted. When the applied electric current per unit of body surface area is too high, skin burn may be caused. When the stimulation frequency is too high, muscle fatigue may be caused. Time of treatment is not restricted specifically. However, if ATP consumption rate exceeds ATP generation rate, muscle cell will generate ATP via anaerobic respiration and make the patient feel tired and uncomfortable.